Blood processing systems and methods that employ an in-line leukofilter mounted in a restraining fixture

ABSTRACT

Systems and methods separate blood cells from whole blood and pump the separated blood cells through an in-line leukofilter to a blood cell storage container. The leukofilter comprises a filtration medium enclosed within a flexile housing. The systems and methods include a fixture to restrain expansion of the flexible filter housing during operation of the pump. The fixture includes a bracket to enable its releasable attachment to the blood processing device employed to carry out the separation process.

RELATED APPLICATION

[0001] This application is a continuation-in-part of co-pending U.S.patent application Ser. No. 09/389,504, filed Sep. 3, 1999, and entitled“Blood Separation Systems and Methods Using a Multiple Function PumpStation to Perform Different On-Line Processing Tasks,” which isincorporated herein by reference.

FIELD OF THE INVENTION

[0002] This invention relates to systems and methods for processing andcollecting blood, blood constituents, or other suspensions of cellularmaterial.

BACKGROUND OF THE INVENTION

[0003] Today people routinely separate whole blood, usually bycentrifugation, into its various therapeutic components, such as redblood cells, platelets, and plasma.

[0004] Conventional blood processing methods use durable centrifugeequipment in association with single use, sterile processing systems,typically made of plastic. The operator loads the disposable systemsupon the centrifuge before processing and removes them afterwards.

[0005] Conventional blood centrifuges are of a size that does not permiteasy transport between collection sites. Furthermore, loading andunloading operations can sometimes be time consuming and tedious.

[0006] In addition, a need exists for further improved systems andmethods for collecting blood components in a way that lends itself touse in high volume, on line blood collection environments, where higheryields of critically needed cellular blood components, like plasma, redblood cells, and platelets, can be realized in reasonable shortprocessing times.

[0007] The operational and performance demands upon such fluidprocessing systems become more complex and sophisticated, even as thedemand for smaller and more portable systems intensifies. The needtherefore exists for automated blood processing controllers that cangather and generate more detailed information and control signals to aidthe operator in maximizing processing and separation efficiencies.

SUMMARY OF THE INVENTION

[0008] The invention provides systems and methods for processing bloodand blood constituents that lend themselves to portable, flexibleprocessing platforms equipped with straightforward and accurate controlfunctions. One aspect of the invention provides a blood processingsystem comprising a blood processing set and a blood processing device.

[0009] The blood processing set includes a donor flow channel to conveyblood from a donor. The set also includes a blood processing flowchannel including a blood separation chamber to centrifugally separateblood cells from donor whole blood. The set further includes a bloodcomponent collection flow channel including a blood cell storagecontainer and an in-line filter to remove leukocytes from the bloodcells before entering the blood cell storage container. The in-linefilter includes a flexible housing that encloses a filter medium.

[0010] The blood processing device includes a pump station adapted to beplaced into communication with the donor flow channel, the bloodprocessing flow channel, and the blood component collection flowchannel. The device also includes a centrifuge station adapted tosupport the blood separation chamber and to rotate the blood separationchamber. The device further includes a controller to operate the pumpstation in multiple modes. One mode is a processing mode, during whichthe pump station is operated to convey whole blood in the donor flowchannel into the blood processing flow channel for separation of theblood cells in the blood separation chamber. Another mode is acollection mode, during which the pump station is operated to convey atleast some of the blood cells in the blood processing flow channel intothe blood component collection flow channel for on-line removal ofleukocytes and collection in the blood cell storage container.

[0011] The system also includes a fixture to restrain expansion of thefilter housing during operation of the pump station in the collectionmode. The fixture includes a bracket to enable releasable attachment ofthe fixture to the blood processing device.

[0012] Other features and advantages of the inventions are set forth inthe following specification and attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013]FIG. 1 is a perspective view of a fluid processing system thatembodies features of the invention, with the doors to the centrifugestation and pump and valve station being shown open to accommodatemounting of a fluid processing set;

[0014]FIG. 2 is a perspective view of the system shown in FIG. 1, withthe doors to the centrifuge station and pump and valve station beingshown closed as they would be during fluid processing operations;

[0015]FIG. 3 is a schematic view of a representative blood processingcircuit formed by the fluid processing set shown in FIGS. 1 and 2;

[0016]FIG. 4 is a perspective view of a blood processing chamber andassociated fluid conveying umbilicus that form a part of the fluidprocessing set shown in FIGS. 1 and 2;

[0017]FIG. 5 is an exploded top perspective view of the of a two-partmolded centrifugal blood processing container, which can form a part ofthe fluid processing set used in association with the device shown inFIGS. 1 and 2;

[0018]FIG. 6 is a bottom perspective view of the molded processingcontainer shown in FIG. 5;

[0019]FIG. 7 is a side section view of the molded processing containershown in FIG. 5, after connection of an umbilicus;

[0020]FIG. 8 is a side section view of a three-part molded centrifugalblood processing container which can form a part of the fluid processingset used in association with the device shown in FIGS. 1 and 2;

[0021]FIG. 9 is a top view of the molded processing container shown inFIG. 5, showing certain details of the separation channel;

[0022]FIG. 10 is an exploded perspective view of the centrifuge stationand associated centrifuge assembly of the device shown in FIGS. 1 and 2;

[0023]FIG. 11 is an enlarged exploded perspective view of the centrifugeassembly shown in FIG. 10;

[0024]FIG. 12 is a perspective view of the centrifuge assembly fullyassembled and housed in the centrifuge station of the device shown inFIGS. 1 and 2, with the blood processing chamber and associatedumbilicus also mounted on the centrifuge assembly for use;

[0025]FIG. 13 is a perspective view of the rotor plate that forms a partof the centrifuge assembly shown in FIGS. 10 to 12, showing the latchassembly which releasably secures the processing chamber to thecentrifuge assembly, the latch assembly being shown in its chamberretaining position;

[0026]FIG. 14 is a side section view of the rotor plate shown in FIG.13, showing the components of the latching assembly as positioned whenthe latch assembly is in its chamber retaining position;

[0027]FIG. 15 is a side section view of the rotor plate shown in FIG.13, showing the components of the latching assembly as positioned whenthe latch assembly is in its chamber releasing position;

[0028] FIGS. 16 to 18 are a series of perspective view of the centrifugestation of the device shown in FIGS. 1 and 2, showing the sequence ofloading the processing chamber and associated umbilicus on thecentrifuge assembly prior to use;

[0029] FIGS. 19 to 22 are a series of perspective view of the centrifugestation of the device shown in FIGS. 1 and 2, after loading theprocessing chamber and associated umbilicus on the centrifuge assembly,showing at ninety degree intervals the travel of the umbilicus to impartrotation to the processing chamber, as driven and restrained byumbilicus support members carried by the yoke;

[0030]FIG. 23 is a schematic view of a fluid processing circuit of thetype shown in FIG. 3, showing certain details of the arrangement ofpumps that convey blood and fluid through the circuit;

[0031]FIGS. 24A and 24B are perspective views of a leukofilter that canform a part of the fluid process circuit shown in FIGS. 3 and 23, theleukofilter comprising a filter media enclosed between two flexiblesheets of plastic material, FIG. 24A showing the leukofilter in anexploded view and FIG. 24B showing the leukofilter in an assembled view;

[0032]FIGS. 25A and 25B are perspective views of the leukofilter shownin FIG. 24B in association with a fixture that retains the leukofilterduring use, FIG. 25A showing the leukofilter being inserted into anopened fixture and FIG. 25B showing the leukofilter retained for usewithin a closed fixture;

[0033]FIG. 26 is a perspective view of a device of a type of shown inFIGS. 1 and 2, with the lid of the device closed to also reveal thelocation of various components and a leukofilter holder carried on theexterior of the lid;

[0034]FIG. 27 is a partial perspective view of a side of the base of adevice of a type shown in FIGS. 1 and 2, showing a holder for supportingthe leukofilter retaining fixture shown in FIGS. 25A and 252 duringfluid processing operations;

[0035]FIG. 28 is a view of one side of the leukofilter retaining fixtureof a type shown in FIGS. 25A and 25B, showing a mounting bracket thatcan be used to secure the leukofilter either to the lid-mountedreceptacle shown in FIG. 26 or the base-mounted holder shown in FIG. 27;and

[0036]FIG. 29 is an exploded perspective view of a cassette, which canform a part of the processing set used in association with theprocessing device shown in FIGS. 1 and 2, and the pump and valve stationon the processing device, which receives the cassette for use.

[0037] The invention may be embodied in several forms without departingfrom its spirit or essential characteristics. The scope of the inventionis defined in the appended claims, rather than in the specificdescription preceding them. All embodiments that fall within the meaningand range of equivalency of the claims are therefore intended to beembraced by the claims.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0038]FIG. 1 shows a fluid processing system 10 that embodies thefeatures of the invention. The system 10 can be used for processingvarious fluids.

[0039] The system 10 is particularly well suited for processing wholeblood and other suspensions of biological cellular materials.Accordingly, the illustrated embodiment shows the system 10 used forthis purpose.

[0040] I. System Overview

[0041] The system 10 includes three principal components. These are: (i)a liquid and blood flow set 12 (shown schematically in FIG. 3); (ii) ablood processing device 14 (see FIGS. 1 and 2), which interacts with theflow set 12 to cause separation and collection of one or more bloodcomponents; and (iii) a controller 16 carried on board the device 14,which governs the interaction to perform a blood processing andcollection procedure selected by the operator.

[0042] A. The Processing Device and Controller

[0043] The blood processing device 14 and controller 16 are intended tobe durable items capable of long term use. In the illustrated andpreferred embodiment, the blood processing device 14 and controller 16are mounted inside a portable housing or case 36. The case 36 presents acompact footprint, suited for set up and operation upon a table top orother relatively small surface. The case 36 is also intended to betransported easily to a collection site.

[0044] The case 36 includes a base 38 and a hinged lid 40, which opensfor use (as FIG. 1 shows). In use, the base 38 is intended to rest in agenerally horizontal support surface. The lid 40 also closes fortransport (see FIG. 26).

[0045] The case 36 can be formed into a desired configuration, e.g., bymolding. The case 36 is preferably made from a lightweight, yet durable,plastic material.

[0046] The controller 16 carries out process control and monitoringfunctions for the system 10. The controller 16 comprises a mainprocessing unit (MPU), which can comprise, e.g., a Pentium™ typemicroprocessor made by Intel Corporation, although other types ofconventional microprocessors can be used. The MPU can be mounted insidethe lid 40 of the case 36.

[0047] Preferably, the controller 16 also includes an interactive userinterface 260, which allows the operator to view and comprehendinformation regarding the operation of the system 10. In the illustratedembodiment, the interface 260 includes an interface screen carried inthe lid 40, which displays information for viewing by the operator inalpha-numeric format and as graphical images.

[0048] Further details of the controller 16 can be found in Nayak et al,U.S. Pat. No. 6,261,065, which is incorporated herein by reference.Further details of the interface can be found in Lyle et al, U.S. Pat.No. 5,581,687, which is also incorporated herein by reference.

[0049] As FIG. 26 shows, the lid 40 can be used to support otherinput/outputs to couple other external devices to the controller 16 orother components of the device 14. For example, an ethernet port 50, oran input 52 for a bar code reader or the like (for scanning informationinto the controller 16), or a diagnostic port 54, or a port 56 to becoupled to a pressure cuff 58 (see FIG. 3), or a system transducercalibration port 60, can all be conveniently mounted for access onexterior of the lid 40, or elsewhere on the case 36 of the device 14.

[0050] B. The Flow Set

[0051] The flow set 12 (see FIG. 3), is intended to be a sterile, singleuse, disposable item. Before beginning a given blood processing andcollection procedure, the operator loads various components of the flowset 12 in the case 36 in association with the device 14 (as FIGS. 1 and2 show). The controller 16 implements the procedure based upon presetprotocols, taking into account other input from the operator. Uponcompleting the procedure, the operator removes the flow set 12 fromassociation with the device 14. The portion of the set 12 holding thecollected blood component or components are removed from the case 36 andretained for storage, transfusion, or further processing. The remainderof the set 12 is removed from the case 36 and discarded.

[0052] The flow set 12 can take various forms. In the illustratedembodiment (see FIGS. 1 and 3), the flow set includes a blood processingchamber 18 designed for use in association with a centrifuge.Accordingly, the processing device 14 includes a centrifuge station 20(see FIG. 1), which receives the processing chamber 18 for use (see FIG.12).

[0053] As FIG. 1 shows, the centrifuge station 20 comprises acompartment 21 formed in the base 38. The centrifuge station 20 includesa door 22, which opens and closes the compartment 21. The door 22 opens(as FIG. 1 shows) to allow loading of the processing chamber 18 into thecompartment 21. The door 22 closes (as FIG. 2 shows) to enclose theprocessing chamber 18 within the compartment 21 during operation.

[0054] The centrifuge station 20 rotates the processing chamber 18. Whenrotated, the processing chamber 18 centrifugally separates whole bloodreceived from a donor into component parts, e.g., red blood cells,plasma, and platelets.

[0055] In the illustrated embodiment, the set 12 also includes a fluidpressure actuated cassette 28 (see FIG. 29). The cassette 28 provides acentralized, programmable, integrated platform for all the pumping andvalving functions required for a given blood processing procedure. Inthe illustrated embodiment, the fluid pressure comprises positive andnegative pneumatic pressure. Other types of fluid pressure can be used.

[0056] The cassette 28 can take various forms. In a preferred embodiment(see FIG. 29), the cassette 28 comprises an injection molded body 200made of a rigid medical grade plastic material. Flexible diaphragms 202,preferably made of flexible sheets of medical grade plastic, overlay thefront side and back sides of the cassette 28. The diaphragms are sealedabout their peripheries to the peripheral edges of the front and backsides of the cassette 28.

[0057] As FIG. 29 shows, the cassette 28 has an array of interiorcavities formed on both the front and back sides The interior cavitiesdefine pneumatic pump stations (schematically designated PS in FIG. 3),which are interconnected by a pattern of fluid flow paths (schematicallydesignated FP in FIG. 3) through an array of in line, pneumatic valves(schematically designated V in FIG. 3).

[0058] As FIGS. 1 and 29 show, the cassette 28 interacts with apneumatic actuated pump and valve station 30, which is mounted in thelid of the 40 of the case 36. The pump and valve station 30 includes acassette holder 216. A door 32 is hinged to move with respect to thecassette holder 216 between an opened position, exposing the cassetteholder 216 (shown in FIG. 1) for loading and unloading the cassette 28,and a closed position, enclosing the cassette 28 within the pump andvalve station 30 for use (shown in FIG. 2). The pump and valve station30 includes pneumatic actuator ports 204 (see FIG. 29) that applypositive and negative pneumatic pressure upon the diaphragms of thecassette 28. The pneumatic pressures displace the diaphragms 202 withrespect to the pump chambers and valves, to thereby direct liquid flowthrough the cassette 28.

[0059] Further details of the cassette 28 and the operation of the pumpand valve station 30 can be found in Nayak et al, U.S. Pat. No.6,261,065, which is incorporated herein by reference.

[0060] Referred back to FIG. 3, the flow set 16 also includes an arrayof tubes and containers in flow communication with the cassette 28. Thearrangement of tubes and containers can vary according to the processingobjectives. The system 10 can be operated to collect red blood cells,plasma, red blood cells and plasma, and platelets.

[0061] In the illustrated embodiment, the flow set 16 is arranged tosupport the centrifugal collection of two units of red blood cells(about 360 ml), and to filter the red blood cells to reduce the numberof leukocytes prior to storage. During this procedure, whole blood froma donor is centrifugally processed in the chamber 18 into red bloodcells (in which a majority of the leukocytes resides) and a plasmaconstituent (in which a majority of the platelets resides). The plasmaconstituent is returned to the donor, while the targeted volume of redblood cells is collected, filtered to reduce the population ofleukocytes, and placed into containers for storage mixed with a redblood cell storage solution.

[0062] In this configuration (see FIG. 3), the flow set 16 includes adonor tube 266 having an attached phlebotomy needle 268. The donor tube266 is coupled to a port of the cassette 28.

[0063] As FIG. 3 shows, a pressure cuff 58 is desirable used to enhancevenous blood flow through the phlebotomy needle 268 during bloodprocessing. The pressure cuff 58 is coupled to the pressure cuff port 56on the lid 40 (as previously described), and the pressure supplied tothe cuff 58 is desirably controlled by the controller 16. The controller16 can also operate a vein pressure display 62 (see FIG. 26), whichshows vein pressure at the pressure cuff 56.

[0064] An anticoagulant tube 270 is coupled to the phlebotomy needle268. The anticoagulant tube 270 is coupled to another cassette port. Acontainer 276 holding anticoagulant is coupled via a tube 274 to anothercassette port.

[0065] A container 288 holding saline is coupled via a tube 284 toanother cassette port.

[0066] The set 16 further includes tubes 290, 292, 294, which extend toan umbilicus 296. When installed in the processing station, theumbilicus 296 links the rotating processing chamber 18 with the cassette28 without need for rotating seals. In a preferred embodiment, theumbilicus 296 is made from rotational-stress-resistant Hytrel®copolyester elastomers (DuPont). Further details of the construction ofthe umbilicus 296 will be provided later.

[0067] The tubes 290, 292, and 294 are coupled, respectively, to othercassette ports. The tube 290 conveys whole blood into the processingchamber 18. The tube 292 conveys plasma constituent from the processingchamber 18. The tube 294 conveys red blood cells from processing chamber18.

[0068] A plasma collection reservoir 304 is coupled by a tube 302 to acassette port. The collection reservoir 304 is intended, in use, toserve as a reservoir for the plasma constituent during processing priorto its return to the donor.

[0069] A red blood cell collection reservoir 308 is coupled by a tube306 to a cassette port. The collection reservoir 308 is intended, inuse, to receive red blood cells during processing for storage.

[0070] Two red blood cell storage containers 307 and 309 are coupled bya tube 311 to another cassette port. A leukocyte reduction filter 313 iscarried in line by the tube 311. During processing, red blood cells aretransferred from the red blood cell collection reservoir 308 through thefilter 313 into the storage containers 307 and 309.

[0071] A container 280 holding a red blood cell storage or additivesolution is coupled via a tube 278 to another cassette port. The redblood cell storage solution is metered into the red blood cells as theyare conveyed from the container 308, through the filter 313, into thestorage containers 307 and 309. Further details of this aspect of thecollection process will be described later.

[0072] A whole blood reservoir 312 is coupled by a tube 310 to acassette port. The collection container 312 is intended, in use, toserve as a reservoir for whole blood during processing.

[0073] In the illustrated embodiment, the set 16 further includes afixture 338 (see FIG. 4) to hold the tubes 292 and 294 in viewingalignment with an optical sensing station 332 in the base 36 (see FIG.12). The sensing station 332 optically monitors the presence or absenceof targeted blood components (e.g., platelets and red blood cells)conveyed by the tubes 292 and 294. The sensing station 332 providesoutput reflecting the presence or absence of such blood components. Thisoutput is conveyed to the controller 16. The controller 16 processes theoutput and generates signals to control processing events based, inpart, upon the optically sensed events. Further details of the operationof the controller to control processing events based upon opticalsensing can be found in Nayak et al, U.S. Pat. No. 6,261,065, which isincorporated herein by reference.

[0074] As FIG. 12 shows, the sensing station 332 is desirably locatedwithin the confines of the centrifuge station 20. This arrangementminimizes the fluid volume of components leaving the chamber beforemonitoring by the sensing station 332.

[0075] The fixture 338 gathers the tubes 292 and 294 in a compact,organized, side-by-side array, to be placed and removed as a group inassociation with the sensing station 332. In the illustrated embodiment,the fixture 338 also holds the tube 290, which conveys whole blood intothe processing chamber 18, even though no associated sensor is provided.The fixture 338 serves to gather and hold all tubes 290, 292, and 294that are coupled to the umbilicus 296 in a compact and easily handledbundle.

[0076] The fixture 338 can be an integral part of the umbilicus 296,formed, e.g., by over molding. Alternatively, the fixture 338 can be aseparately fabricated part, which snap fits about the tubes 290, 292,and 294 for use.

[0077] As FIGS. 1 and 2 also show, the case 36 contains other componentscompactly arranged to aid blood processing. In addition to thecentrifuge station 20 and pump and valve station 30, already described,the case 36 includes a weigh station 238 and one or more trays 212 orhangers 248 for containers. The arrangement of these components in thecase 36 can vary.

[0078] In the illustrated embodiment, the weigh station 238 comprises aseries of container hangers/weigh sensors 246 arranged along the top ofthe lid 40. In use, the containers 304, 308, 312 are suspended on thehangers/weigh sensors 246.

[0079] The holding trays 212 comprise molded recesses in the base 38.The trays 212 accommodate the containers 276 (containing anticoagulant)and 280 (containing the red blood cell additive solution) . In theillustrated embodiment, an additional swing-out side hanger 248 is alsoprovided on the side of the lid 40. The hanger 248 (see FIG. 2) supportsthe container 288 (containing saline) during processing. Other swing outhangers 249 support the red blood cells storage containers 307 and 309.

[0080] In the illustrated embodiment, the tray 212 holding the container276 and the hanger 248 also include weigh sensors 246.

[0081] As blood or liquids are received into and/or dispensed from thecontainers during processing, the weigh sensors 246 provide outputreflecting weight changes over time. This output is conveyed to thecontroller 16. The controller 16 processes the incremental weightchanges to derive fluid processing volumes. The controller generatessignals to control processing events based, in part, upon the derivedprocessing volumes. Further details of the operation of the controllerto control processing events can be found in Nayak et al, U.S. Pat. No.6,261,065, which is incorporated herein by reference.

[0082] C. The Centrifugal Processing Chamber

[0083] FIGS. 5 to 7 show an embodiment of the centrifugal processingchamber 18, which can be used in association with the system 10 shown inFIG. 1 to perform the intended red blood cell collection procedure. Inthe illustrated embodiment, the processing chamber 18 is preformed in adesired shape and configuration, e.g., by injection molding, from arigid, biocompatible plastic material, such as a non-plasticized medicalgrade acrilonitrile-butadienestyrene (ABS).

[0084] In one arrangement, the chamber 18 can be fabricated in twoseparately molded pieces; namely (as FIGS. 5 to 7 show), a base 388 anda lid 150. The base 388 includes a center hub 120. The hub 120 issurrounded radially by inside and outside annular walls 122 and 124.Between them, the inside and outside annular walls 122 and 124 define acircumferential blood separation channel 126. A molded annular wall 148closes the bottom of the channel 126.

[0085] The top of the channel 126 is closed by the separately molded,flat lid 150 (which is shown separated in FIG. 5 for the purpose ofillustration). During assembly (see FIG. 7), the lid 150 is secured tothe top of the chamber 18, e.g., by use of a cylindrical sonic weldinghorn.

[0086] All contours, ports, channels, and walls that affect the bloodseparation process may be preformed in the base 388 in a single,injection molded operation, during which molding mandrels are insertedand removed through the open end of the base 388 (shown in FIG. 5). Thelid 150 comprises a simple flat part that can be easily welded to theopen end of the base 388 to close it after molding. Because all featuresthat affect the separation process are incorporated into one injectionmolded component, any tolerance differences between the base 388 and thelid 150 will not affect the separation efficiencies of the chamber 18.

[0087] The contours, ports, channels, and walls that are preformed inthe base 388 may create surfaces within the base 388 that do not readilypermit the insertion and removal of molding mandrels through a singleend of the base 388. In this arrangement, the base 388 can be formed byseparate molded parts, either by nesting cup shaped subassemblies or twosymmetric halves.

[0088] Alternatively, molding mandrels can be inserted and removed fromboth ends of the base 388. In this arrangement (see FIG. 8), the chamber18 can be molded in three pieces; namely, the base 388, the lid 150(which closes one end of the base 388 through which top molding mandrelsare inserted and removed), and a separately molded insert 151 (whichcloses the other end of the base 388 through which bottom moldingmandrels are inserted and removed.

[0089] The contours, ports, channels, and walls that are preformed inthe base 388 can vary.

[0090] As seen in FIG. 9, in one arrangement, the inside annular wall122 is open between one pair of stiffening walls. The opposingstiffening walls form an open interior region 134 in the hub 120, whichcommunicates with the channel 126. Blood and fluids are introduced fromthe umbilicus 296 into and out of the separation channel 126 throughthis region 134.

[0091] In this embodiment (as FIG. 9 shows), a molded interior wall 136formed inside the region 134 extends entirely across the channel 126,joining the outside annular wall 124. The wall 136 forms a terminus inthe separation channel 126, which interrupts flow circumferentiallyalong the channel 126 during separation.

[0092] Additional molded interior walls divide the region 124 into threepassages 142, 144, and 146. The passages 142, 144, and 146 extend fromthe hub 120 and communicate with the channel 126 on opposite sides ofthe terminus wall 136. Blood and other fluids are directed from the hub120 into and out of the channel 126 through these passages 142, 144, and146.

[0093] The underside of the base 388 (see FIG. 7) includes a shapedreceptacle 179. The far end of the umbilicus 296 includes a shaped mount178 (see FIGS. 24 and 24A). The mount 178 is shaped to correspond to theshape of the receptacle 179. The mount 178 can thus be plugged into thereceptacle 179 (as FIG. 7 shows), to couple the umbilicus 296 in fluidcommunication with the channel 126.

[0094] The mount 178 is desirably made from a material that canwithstand considerable flexing and twisting, to which the mount 178 canbe subjected during use, e.g., Hytrel® 3078 copolyester elastomer(DuPont). The dimensions of the shaped receptacle 179 and the shapedmount 178 are preferably selected to provide a tight, dry press fit, tothereby avoid the need for solvent bonding or ultrasonic weldingtechniques between the mount 178 and the base 388 (which can thereforebe formed from an incompatible material, such as ABS plastic).

[0095] D. The Centrifuge Assembly

[0096] The centrifuge station 20 (see FIG. 10) includes a centrifugeassembly 48. The centrifuge assembly 48 is constructed to receive andsupport the molded processing chamber 18 and umbilicus 296 for use.

[0097] As illustrated (see FIGS. 10 and 11), the centrifuge assembly 48includes a yoke 154 having bottom, top, and side walls 156, 158, 160.The yoke 154 spins on a bearing element 162 (FIG. 11) attached to thebottom wall 156. An electric drive motor 164 is coupled to the bottomwall 156 of the yoke 154, to rotate the yoke 154 about an axis 64. Inthe illustrated embodiment, the axis 64 is essentially horizontal (seeFIG. 1), although other angular orientations can be used.

[0098] A rotor plate 166 (see FIG. 11) spins within the yoke 154 aboutits own bearing element 168, which is attached to the top wall 158 ofthe yoke 154. The rotor plate 166 spins about an axis that is generallyaligned with the axis of rotation 64 of the yoke 154.

[0099] As FIG. 7 best shows, the top of the processing chamber 18includes an annular lip 380, to which the lid 150 is secured. As FIG. 12shows, the rotor plate 166 includes a latching assembly 382 thatremovably grips the lip 380, to secure the processing chamber 18 on therotor plate 166 for rotation.

[0100] The configuration of the latching assembly 382 can vary. In theillustrated embodiment (see FIGS. 13 to 15), the latching assembly 382includes a latch arm 66 pivotally mounted on a pin in a peripheralrecess 68 in the rotor plate 166. The latch arm 66 pivots between aretaining position (shown in FIGS. 13 and 14) and a releasing position(shown in FIG. 15).

[0101] In the retaining position (see FIG. 14), an annular groove 70 onthe underside of the latch arm 66 engages the annular lip 380 of theprocessing chamber 18. The annular groove 70 on the latch arm 70coincides with an annular groove 71 that encircles the top interiorsurface of the rotor plate 166. The engagement of the lip 380 within thegroove 70/71 secures the processing chamber 18 to the rotor plate 166.

[0102] In the releasing position (see FIG. 15), the annular groove 70 isswung free of engagement of the annular lip 380. This lack of engagementallows release of the processing chamber 18 from the remainder of thegroove 71 in the rotor plate 166.

[0103] In the illustrated embodiment, the latching assembly 382 includesa sliding pawl 72 carried in a radial track 74 on the top of the rotorplate. In the track 74, the pawl 72 slides radially toward and away fromthe latch arm 66.

[0104] When the latch arm 66 is in its retaining position and the pawl72 is located in a radial position adjacent the latch arm 66 (see FIG.14), a finger 76 on the pawl 72 slips into and engages a cam recess 78in the latch arm 66. The engagement between the pawl finger 76 and latcharm cam recess 78 physically resists movement of the latch arm 66 towardthe releasing position, thereby locking the latch arm 66 in theretaining position.

[0105] A spring 80 within the pawl 72 normally biases the pawl 72 towardthis radial position adjacent the latch arm 66, where engagement betweenthe pawl finger 76 and latch arm cam recess 78 can occur. The latch arm66 is thereby normally held by the pawl 72 in a locked, retainingposition, to hold the processing chamber 18 during use.

[0106] The pawl 72 can be manually moved against the bias of the spring80 radially away from its position adjacent the latch arm 66 (see FIG.15). During this movement, the finger 76 on the pawl 72 slips free ofthe cam recess 78 in the latch arm 66. Free of engagement between thepawl finger 76 and latch arm cam recess 78, the latch arm 66 is unlockedand can be pivoted toward its releasing position. In the absence ofmanual force against the bias of the spring 80, the pawl 72 returns byspring force toward its position adjacent the latch arm 66, to lock thelatch arm 66 in the chamber retaining position.

[0107] In the illustrated embodiment (see FIG. 13), the top wall 158 ofthe yoke 154 carries a downward depending collar 82. The collar 82rotates in unison with the yoke 154, relative to the rotor plate 166.The collar 82 includes a sidewall 84 that is continuous, except for acut away or open region 86.

[0108] As FIG. 17 best shows, the pawl 72 includes an upstanding keyelement 88. The sidewall 84 of the collar 82 is located in the radialpath that the key element 88 travels when the pawl 72 is manually movedagainst the bias of the spring 80 radially away from its positionadjacent the latch arm 66. The key element 88 abuts against the collarsidewall 84, to inhibit movement of the pawl 72 in this direction,unless the open region 86 is aligned with the key element 88, as shownin FIGS. 13 and 15. The open region 86 accommodates passage of the keyelement 88, permitting manual movement of the pawl 72 against the biasof the spring 80 radially away from its position adjacent the latch arm66, thereby allowing the latch arm 66 to pivot into its releasingposition.

[0109] The interference between the collar sidewall 84 and the keyelement 88 of the pawl 72 prevents manual movement of the pawl 72 awayfrom the latch arm 66, to unlock the latch arm 66 for movement into itsreleasing position, unless the open region 86 and the key element 88register. The open region 86 is aligned on the yoke 154 so that thisregistration between the open region 86 and the key element 88 occursonly when the rotor plate 166 is in a prescribed rotational positionrelative to the ybke 154. In this position (see FIG. 12), the sidewalls160 of the yoke 154 are located generally parallel to the plane of theopening to the compartment, providing open access to the interior of theyoke 154. In this position (see FIG. 16), the processing chamber 18 canbe freely placed without interference into the interior of the yoke 154,and loaded onto the rotor plate 166. In this position, uninhibitedmanual movement of the pawl 72 allows the operator to pivot the latcharm 66 into its releasing position, to bring the lid 150 of the chamber18 into contact against the rotor plate 166. Subsequent release of thepawl 72 returns the pawl 72 toward the latch arm 66 and allows theoperator to lock the latch arm 66 in its retaining position about thelip 380 of the chamber 18. The reverse sequence is accommodated when itis time to remove the processing chamber 18 from the rotor plate 166.

[0110] This arrangement makes possible a straightforward sequence ofacts to load the processing chamber 18 for use and to unload theprocessing chamber 18 after use (see FIG. 16). As FIGS. 17 and 18further show, easy loading of the umbilicus 296 is also made possible intandem with fitting the processing chamber 18 to the rotor plate 166.

[0111] A sheath 182 on the near end of the umbilicus 296 fits into apreformed, recessed pocket 184 in the centrifuge station 20. The pocket184 holds the near end of the umbilicus 296 in a non-rotating stationaryposition aligned with the mutually aligned rotational axes 64 of theyoke 154 and rotor plate 166.

[0112] The preformed pocket 184 is also shaped to accommodate loading ofthe fixture 338 at the same time the sheath 182 is inserted. The tubes290, 292, and 294 are thereby placed and removed as a group inassociation with the sensing station 332, which is located within thepocket 184.

[0113] Umbilicus support members 186 and 187 (see FIG. 12) are carriedby a side wall 160 of the yoke 154. When the rotor plate 166 is locatedin its prescribed rotational position to enable easy loading of thechamber 18 (see FIGS. 17 and 18), the support members 186 and 187 arepresented on the left side of the processing chamber 18 to receive theumbilicus 296 at the same time that the sheath 182 and fixture 338 aremanipulated for fitting into the pocket 184.

[0114] As FIG. 19 shows, one member 186 receives the mid portion of theumbilicus 296. The member 186 includes a surface 188 against which themid portion of the umbilicus 296 rests. The surface 188 forms a channelthat extends generally parallel to the rotational axis 64 and thataccommodates passage of the mid portion of the umbilicus 296. Thesurface 188 inhibits travel of the mid portion of the umbilicus 296 inradial directions toward and away from the rotational axis 64. However,the surface 188 permits rotation or twisting of the umbilicus 296 aboutits own axis.

[0115] The other member 187 receives the upper portion of the umbilicus296. The member 187 includes a surface 190 against which the upperportion of the umbilicus 296 rests. The surface 190 forms a channelinclined toward the top wall 158 of the yoke 154. The surface 190 guidesthe upper portion of the umbilicus 296 toward the recessed pocket 184,which is located axially above the top wall 158 of the yoke 154, wherethe umbilicus sheath 182 and fixture 338 are fitted. Like the surface188, the surface 190 inhibits travel of the upper portion of theumbilicus 296 in radial directions toward and away from the rotationalaxis 64. However, like the surface 188, the surface 190 permits rotationor twisting of the umbilicus 296 about its own axis.

[0116] Closing the centrifuge station door 20 positions a holdingbracket 90 on the underside of the door 20 in registry with the sheath182 (see FIGS. 17 and 18). Another holding bracket 92 on the undersideof the door 20 is positioned in registry with the fixture 338 when thedoor 20 is closed. A releasable latch 94 preferably holds the door shutduring operation of the centrifuge assembly 48.

[0117] During operation of the centrifuge assembly 48 (see FIGS. 19 to22), the support members 186 and 187 carry the umbilicus 296 so thatrotation of the yoke 154 also rotates the umbilicus 296 in tandem aboutthe yoke axis. Constrained within the pocket 184 at its near end (i.e.,at the sheath 182) and coupled to the chamber 16 at its far end (i.e.,by the mount 178), the umbilicus 296 twists upon the surfaces 188 and190 about its own axis as it rotates about the yoke axis 64, even as thesurfaces 188 and 190 inhibit radial travel of the umbilicus relative tothe rotation axis 64. The twirling of the umbilicus 296 about its axisas it rotates upon the surfaces 188 and 190 at one omega with the yoke154 (typically at a speed of about 2250 RPM) imparts a two omegarotation to the processing chamber 18 secured for rotation on the rotorplate 166.

[0118] The relative rotation of the yoke 154 at a one omega rotationalspeed and the rotor plate 166 at a two omega rotational speed, keeps theumbilicus 296 untwisted, avoiding the need for rotating seals. Theillustrated arrangement also allows a single drive motor 164 to impartrotation, through the umbilicus 296, to the mutually rotating yoke 154and processing chamber 18 carried on the rotor plate 166. Furtherdetails of this arrangement are disclosed in Brown et al U.S. Pat. No.4,120,449, which is incorporated herein by reference.

[0119] The umbilicus 296 can stretch in response to the rotationalforces it encounters. The dimensions of a given umbilicus 296 are alsosubject to normal manufacturing tolerances. These factors affect theflight radius of the umbilicus 296 during use; as well as the stressencountered by the mount 178 at the far end of the umbilicus 296, whichserves as the two omega torque transmitter to drive the processingchamber 18; as well as the lateral loads acting on the centrifuge andmotor bearings.

[0120] As FIGS. 19 to 22 show, the support members 186 and 187 on theyoke serve to physically confine the flight of the umbilicus 296 betweenthe one omega region (mid portion) and two omega region (far endportion), as well as between the one omega region (mid portion) and zeroomega region (near end portion) of the umbilicus 296. By confining theumbilicus 296 to a predefined radial distance from and radialorientation with respect to the rotational axis of the centrifugeassembly 48, the support members 186 and 187 serve to attenuate thefactors that can affect umbilicus performance and endurance.

[0121] The support members 186 and 187 make possible a bearing-lessumbilicus assembly with no moving parts, while leading to reduced stressat the two omega torque region, where stresses tend to be greatest. Thesurfaces 188 and 190 of the support members 186 and 187 can be formedand oriented to accommodate rotation of the umbilicus 296 and thedriving of the processing chamber 18 in either clockwise orcounterclockwise directions.

[0122] In the illustrated embodiment, the surfaces 188 and 190 of thesupport members 186 and 187 are preferably fabricated from a lowfriction material, to thereby eliminate the need for externallubrication or rotating bearings on the umbilicus 296 itself. Thematerial used can, e.g., comprise Teflon® polytetrafluoroethylenematerial (DuPont) or an ultra high molecular weight polyethylene. Madefrom such materials, the surfaces 188 and 190 minimize umbilicus drivefriction and the presence of particulate matter due to umbilicus wear.

[0123] In a representative embodiment (see FIG. 4), the umbilicus 296desirably comprises a two layer co-extruded assembly. The interior orcore layer 96 desirably comprises Hytrel® 4056 copolyester elastomer(DuPont). The outside layer 98 desirably comprises Hytrel® 3078copolyester elastomer (DuPont). The outside layer 98 may comprise arelatively thin extrusion, compared to the core layer 96.

[0124] In this arrangement, the outside layer 98 of Hytrel® 3078copolyester elastomer serves as a compatible interface to accommodateover-molding of the zero omega sheath 182 and the two omega mount 178,which may comprise the same Hytrel® 3078 material or an otherwisecompatible material. Absent material compatibility, solvents (e.g.,methylene chloride) or other forms of surface treatment may be requiredto facilitate a robust bond between these elements and the umbilicus.Hytrel® 3078 material is desired for the sheath 182, and the mount 178because it can withstand considerable flexing and twisting forces, towhich these regions of the umbilicus are subjected during use.

[0125] The core layer 96 of Hytrel® 4056 copolyester elastomer can bereadily solvent bonded to conventional flexible medical grade polyvinyltubing, from which the tubes 290, 292, and 294 are desirably made.

[0126] II. Double Red Blood Cell Collection Procedure

[0127] Use of the set 12 in association with the device 14 andcontroller 16 to conduct a typical double unit red blood cell collectionprocedure will now be described for illustrative purposes.

[0128] A. The Cassette

[0129] The cassette 28 used for a procedure of this type desirablyincludes dual pneumatic pump chambers PP3 and PP4 (see FIG. 23) whichare operated by the controller 16 in tandem to serve as a generalpurpose, donor interface pump. The dual donor interface pump chambersPP3 and PP4 work in parallel. One pump chamber draws fluid, while theother pump chamber expels fluid. The dual pump chambers PP3 and PP4thereby alternate draw and expel functions to provide a uniform outletflow.

[0130] The cassette 28 also desirably includes a pneumatic pump chamberPP5, which serves as a dedicated anticoagulant pump, to drawanticoagulant from the container 276 and meter the anticoagulant intothe blood drawn from the donor.

[0131] The cassette 28 also desirably includes a pneumatic pump chamberPP1 that serves as a dedicated in-process whole blood pump, to conveywhole blood from the reservoir 312 into the processing chamber 18. Thededicated function of the pump chamber PP1 frees the donor interfacepump chambers PP3 and PP4 from the added function of supplying wholeblood to the processing chamber 18. Thus, the in-process whole bloodpump chamber PP1 can maintain a continuous supply of blood to theprocessing chamber 18, while the donor interface pump chambers PP3 andPP4 operate in tandem to simultaneously draw and return blood to thedonor through the single phlebotomy needle. Processing time is therebyminimized.

[0132] The cassette 28 also desirably includes a pneumatic pump chamberPP2 that serves as a plasma pump, to convey plasma from the processingchamber 18. The ability to dedicate separate pumping functions providesa continuous flow of blood into and out of the processing chamber 18, aswell as to and from the donor.

[0133] B. Capacitive Flow Sensing

[0134] The controller 16 desirably includes means for monitoring fluidflow through the pump chambers PP1 to PP5. In the illustratedembodiment, the pump and valve station 30 carries electrode circuits 206associated with each pump chamber PP1 to PP5. The electrode circuits 206can be located, e.g., within the pneumatic actuator ports 204 in thepump and valve station 30 (see FIG. 29) that apply negative and positivepressure to the diaphragms to thereby draw fluid into the chambers PP1to PP5 and expel fluid from the chambers PP1 to PP5. The electrodecircuits 206 are coupled to an electrical source and are in electricalconductive contact with fluids within their respective pump chambers PP1and PP5.

[0135] The passage of electrical energy through each electrode circuit206 creates an electrical field within the respective pump chamber PP1to PP5. Cyclic deflection of the diaphragm associated with a given pumpchamber to draw fluid into and expel fluid from the pump chamber PP1 toPP5 changes the electrical field, resulting in a change in totalcapacitance of the circuit through the electrode. Capacitance increasesas fluid is draw into the pump chamber PP1 to PP5, and capacitancedecreases as fluid is expelled from pump chamber PP1 to PP5.

[0136] In the arrangement, the electrode circuits 206 each includes acapacitive sensor (e.g., a Qprox E2S). The capacitive sensor registerschanges in capacitance for the electrode circuit 206 for each pumpchamber PP1 to PP5. The capacitance signal for a given electrode circuit206 has a high signal magnitude when the pump chamber is filled withliquid, has a low signal magnitude signal when the pump chamber is emptyof fluid, and has a range of intermediate signal magnitudes when thediaphragm occupies intermediate positions.

[0137] At the outset of a blood processing procedure, the controller 16can calibrate the difference between the high and low signal magnitudesfor each sensor to the maximum stroke volume of the respective pumpchamber. The controller 16 can then relate the difference between sensedmaximum and minimum signal values during subsequent draw and expelcycles to fluid volume drawn and expelled through the pump chamber. Thecontroller 16 can sum the fluid volumes pumped over a sample time periodto yield an actual flow rate.

[0138] The controller 16 can compare the actual flow rate to a desiredflow rate. If a deviance exists, the controller 16 can vary pneumaticpressure pulses delivered to the actuators for the pump chambers PP1 toPP5 to minimize the deviance.

[0139] The controller 16 can also operate to detect abnormal operatingconditions based upon the variations in the electric field and togenerate corresponding alarm outputs. The controller 16 can, e.g.,monitor for an increase in the magnitude of the low signal magnitudeover time. The increase in magnitude reflects the presence of air insidea pump chamber.

[0140] For example, the controller 16 can generate a derivative of thesignal output of the sensor 426. Changes in the derivative, or theabsence of a derivative, reflects a partial or complete occlusion offlow through the pump chamber PP1 to PP5. The derivative itself alsovaries in a distinct fashion depending upon whether the occlusion occursat the inlet or outlet of the pump chamber PP1 to PP5.

[0141] 1. Monitoring Vein Flow Conditions

[0142] By using capacitive sensing and by also counting pump strokes(i.e., the application of negative pressure upon the diaphragm of agiven pump chamber to draw fluid into the chamber), the controller 16can also monitor vein flow conditions, and, in particular, assess andrespond to real or potential vein occlusion conditions.

[0143] When blood is pumped from the donor, the donor's vein may showdifficulties in keeping up with the commanded draw rate that operationof the donor pump chambers PP3/PP4 imposes. In the case of restrictedblood flow from the donor, the donor pumps PP3 and PP4 do not fillproperly in response to the commanded sequence of pump strokes. Thecontroller 16 attempts to assess and mediate blood supply interruptionsdue to vein problems before generating a vein occlusion alarm, whichsuspends processing.

[0144] For example, the controller 16 can count the number ofconsecutive attempted pump strokes for which no blood flow into the pumpchambers PP3 and PP4 occurs (which blood flow or absence of blood flowcan be detected by capacitive sensing, as above described). A potentialdonor draw occlusion condition can be deemed to occur when a prescribednumber (e.g., 3) of consecutive incomplete fill donor pump strokes takesplace.

[0145] When a potential donor draw occlusion condition is detected, thecontroller 16 attempts to rectify the condition by increasing pressureof the pressure cuff 58 and/or decreasing the commanded draw rate,before generating a processing-halting vein occlusion alarm.

[0146] More particularly, in a representative implementation, when adonor draw occlusion condition is detected, the controller 16 executes apotential draw occlusion condition function (in shorthand, the“Potential Occlusion Function”). The Potential Occlusion Function firstsuspends the draw for a period of time (e.g. upwards to 20 seconds, anddesirably about 10 seconds) to rest the vein. While the vein rests, thecontroller 16 also increases the pressure cuff pressure by a presetincrement (e.g., upwards to 25 mmHg, and desirably about 10 mmHg),unless cuff pressure, when adjusted, exceeds a prescribed maximum (e.g.,upwards to 100 mmHg, desirably about 70 mmHg). If the prescribed maximumcuff pressure condition exists, no incremental changes to the cuffpressure are made during the prescribed vein rest interval.

[0147] After the prescribed vein rest interval, the Potential OcclusionFunction resets the attempted pump stroke counter to zero and resumesthe draw cycle. The controller 16 monitors the initial series ofconsecutive pump strokes during the resumed draw cycle, up to a firstthreshold number of pump strokes (e.g., 5). The magnitude of the firstthreshold number is larger that the number of consecutive incompletefill donor pump strokes (i.e., 3) that indicate a potential donor drawocclusion condition. The magnitude of the first threshold number isselected to accurate assess, after a potential donor draw occlusioncondition arises, whether a true donor draw occlusion exists. In theillustrated embodiment, if within the first five pump strokes (orwhatever the first threshold number is), three consecutive incompletefill donor pump strokes take place, the controller 16 assumes that atrue donor draw occlusion exists, and thus generates an occlusion alarm.With the generation of an occlusion alarm, the controller 16 suspendsprocessing, until the operator can establish that it is safe to resume.

[0148] If within the first threshold number of pump strokes, threeconsecutive incomplete fill donor pump strokes do not take place, thecontroller 16 assumes that a true vein occlusion may not exist, and thatthe potential occluded flow condition was either transient, or at leastcapable of correction short of suspending the procedure. In this event,the Potential Occlusion Function allows the resumed draw cycle tocontinue beyond the first threshold number of pump strokes up to asecond threshold number of pump strokes (e.g., 20 to 100, and desirableabout 50).

[0149] If at any time between the first threshold number of pump strokesand the second threshold number of pump strokes, three consecutiveincomplete fill donor pump strokes take place, the Potential OcclusionFunction institutes another vein rest interval(e.g. upwards to 20seconds, and desirably about 10 seconds). While the vein rests, thePotential Occlusion Function also again increases the pressure cuffpressure by a preset increment (e.g., upwards to 25 mmHg, and desirablyabout 10 mmHg). While the vein rests, the Potential Occlusion Functionalso lowers the draw rate by a preset decrement (e.g., upwards to 20ml/min, and desirably about 10 ml/min). If the draw rate, when lowered,is less than a prescribed minimum draw rate (e.g., 70 to 90 ml/min), thecontroller 16 generates an occlusion alarm. Otherwise, the PotentialOcclusion Function resets the attempted pump stroke counter to zero, andresumes the draw cycle at the increased cuff pressure and decreased drawrate.

[0150] The controller 16 again monitors the initial series ofconsecutive pump strokes during the resumed draw cycle, up to the firstthreshold number of pump strokes (e.g., 5). If within the firstthreshold number of pump strokes, three consecutive incomplete filldonor pump strokes take place, the controller 16 assumes that a truedonor draw occlusion exists, and thus generates an occlusion alarm andalso suspends processing.

[0151] However, if within the first threshold number of pump strokes,three consecutive incomplete fill donor pump strokes do not take place,the controller 16 allows the resumed draw cycle to continue beyond thefirst threshold number of pump strokes up to the second threshold numberof pump strokes (e.g., 20 to 100, and desirable about 50). If at anytime between the first threshold number of pump strokes and the secondthreshold number of pump strokes, three consecutive incomplete filldonor pump strokes take place, the Potential Occlusion Function againinstitutes another vein rest interval(e.g. upwards to 20 seconds, anddesirably about 10 seconds) . While the vein rests, the PotentialOcclusion Function also again increases the pressure cuff pressure by apreset increment (e.g., upwards to 25 mmHg, and desirably about 10mmHg). While the vein rests, the Potential Occlusion Function also againlowers the draw rate by a preset decrement (e.g., upwards to 20 ml/min,and desirably about 10 ml/min), unless the draw rate, when lowered, isless than a prescribed minimum draw rate (e.g., 70 to 90 ml/min), inwhich case the controller 16 generates an occlusion alarm. Otherwise,the Potential Occlusion Function resets the attempted pump strokecounter to zero, and resumes the draw cycle at the increased cuffpressure and decreased draw rate.

[0152] The controller 16 continues to repeat the steps of the PotentialOcclusion Function, using the first and second pump stroke numberthresholds to gage whether a true vein occlusion exists, and eithergenerating an occlusion alarm if it does, or continuing to attemptremedial action (by increasing cuff pressure and/or decreasing drawrate), or cancelling the potential donor draw occlusion condition whenthree consecutive incomplete fill donor pump strokes are not observedduring either the first or second threshold periods following apotential donor occlusion condition.

[0153] If no three consecutive incomplete fill donor pump strokes takeplace within the second threshold number of strokes following apotential donor draw occlusion condition, the controller 16 assumes thata true vein occlusion does not exist. The draw cycle continues, and thecontroller 16 continues to count pump strokes. If the prescribed number(e.g., 3) of consecutive incomplete fill donor pump strokes subsequentlytakes place, the controller 16 assumes that this event is unrelated toany previous occlusion event condition, and generates a new potentialdonor draw occlusion condition, executing the Potential OcclusionFunction from the start.

[0154] It should be appreciated that the Potential Occlusion Function,as just described, can be used with any blood processing device that hasmeans for detecting when a draw blood pumping command does not result inblood flow through the pump.

[0155] C. Blood Processing Cycles

[0156] Prior to undertaking the double unit red blood cell collectionprocedure, as well as any blood collection procedure, the controller 16conducts an appropriate integrity check of the cassette 28, to determinewhether there are any leaks in the cassette 28. Once the cassetteintegrity check is complete and no leaks are found, the controller 16begins the desired blood collection procedure.

[0157] In general, using the processing chamber shown in FIG. 9), wholeblood is introduced into and separated within the processing chamber 18as it rotates. As the processing chamber 18 rotates (arrow R in FIG. 9),the umbilicus 296 conveys whole blood into the channel 126 through thepassage 146. The whole blood flows in the channel 126 in the samedirection as rotation (which is counterclockwise in FIG. 9).Alternatively, the chamber 18 can be rotated in a direction opposite tothe circumferential flow of whole blood, i.e., clockwise, but rotationin the same direction as circumferential blood flow is preferred.

[0158] The whole blood separates as a result of centrifugal forces. Redblood cells are driven toward the high-G wall 124, while lighter plasmaconstituent is displaced toward the low-G wall 122. In this flowpattern, a dam 384 projects into the channel 126 toward the high-G wall124. The dam 384 prevents passage of plasma, while allowing passage ofred blood cells into a channel 386 recessed in the high-G wall 124. Thechannel 386 directs the red blood cells into the umbilicus 296 throughthe radial passage 144. The plasma constituent is conveyed from thechannel 126 through the radial passage 142 into umbilicus 296.

[0159] 1. Collection Cycle

[0160] During a typical collection cycle of the double unit red bloodcell collection procedure, whole blood drawn from the donor is processedto collect two units of red blood cells, while returning plasma to thedonor. The donor interface pumps PP3/PP4 in the cassette, theanticoagulant pump P5 in the cassette, the in-process pump PP1 in thecassette, and the plasma pump PP2 in the cassette are pneumaticallydriven by the controller 16, in conjunction with associated pneumaticvalves, to draw anticoagulated blood into the in-process container 312,while conveying the blood from the in-process container 312 into theprocessing chamber 18 for separation. This arrangement also removesplasma from the processing chamber into the plasma container 304, whileremoving red blood cells from the processing chamber into the red bloodcell container 308. This phase continues until an incremental volume ofplasma is collected in the plasma collection container 304 (as monitoredby a weigh sensor) or until a targeted volume of red blood cells iscollected in the red blood cell collection container (as monitored by aweigh sensor).

[0161] If the volume of whole blood in the in-process container 312reaches a predetermined maximum threshold before the targeted volume ofeither plasma or red blood cells is collected, the controller 16terminates operation of the donor interface pumps PP3/PP4 to terminatecollection of whole blood in the in-process container 312, while stillcontinuing blood separation. If the volume of whole blood reaches apredetermined minimum threshold in the in-process container 312 duringblood separation, but before the targeted volume of either plasma or redblood cells is collected, the controller 16 returns to drawing wholeblood to thereby allow whole blood to enter the in-process container312. The controller toggles between these two conditions according tothe high and low volume thresholds for the in-process container 312,until the requisite volume of plasma has been collected, or until thetarget volume of red blood cells has been collected, whichever occursfirst.

[0162] 2. Return Cycle

[0163] During a typical return cycle (when the targeted volume of redblood cells has not been collected), the controller 16 operates thedonor interface pumps PP3/PP4 within the cassette 28, the in-processpump PP1 within the cassette, and the plasma pump PP2 within thecassette, in conjunction with associated pneumatic valves, to conveyanticoagulated whole blood from the in-process container 312 into theprocessing chamber 18 for separation, while removing plasma into theplasma container 304 and red blood cells into the red blood cellcontainer 308. This arrangement also conveys plasma from the plasmacontainer 304 to the donor, while also mixing saline from the container288 in line with the returned plasma. The in line mixing of saline withplasma raises the saline temperature and improves donor comfort. Thisphase continues until the plasma container 304 is empty, as monitored bythe weigh sensor.

[0164] If the volume of whole blood in the in-process container 312reaches a specified low threshold before the plasma container 304empties, the controller 16 terminates operation of the in-process pumpPP1 to terminate blood separation. The phase continues until the plasmacontainer 304 empties.

[0165] Upon emptying the plasma container 304, the controller 16conducts another collection cycle. The controller 16 operates insuccessive collection and return cycles until the weigh sensor indicatesthat a desired volume of red blood cells have been collected in the redblood cell collection container 308. The controller 16 terminates thesupply and removal of blood to and from the processing chamber, whileoperating the donor interface pumps PP3/PP4 in the cassette 28 to conveyplasma remaining in the plasma container 304 to the donor. Thecontroller 16 next operates the donor interface pumps PP3/PP4 in thecassette to convey the blood contents remaining in the in-processcontainer 312 to the donor as well as convey saline to the donor, untila prescribed replacement volume amount is infused, as monitored by aweigh sensor.

[0166] 3. In-Line Leukofiltration Cycle

[0167] When the collection of red blood cells and the return of plasmaand residual blood components has been completed, the controller 16switches, either automatically or after prompting the operator, to anin-line leukofiltration cycle. During this cycle, red blood cells areremoved from the red blood cell collection reservoir 308 and conveyedinto the red blood cell storage containers 307 and 308 through theleukocyte removal filter 313. At the same time, a desired volume of redblood cell storage solution from the container 208 is mixed with the redblood cells.

[0168] In the first stage of this cycle, the controller 16 operatesdonor interface pumps PP3/PP4 in the cassette to draw air from the redblood cell storage containers 307 and 309, the filter 313, and the line311, and to transfer this air into the red blood cell collectionreservoir 308. This stage minimizes the volume of air residing in thered blood cell storage containers 307 and 309 before the leukocyteremoval process begins. The stage also provides a volume of air in thered blood cell collection container 308 that can be used purge red bloodcells from the filter 313 into the red blood cell collection containers307 and 309 once the leukocyte removal process is completed.

[0169] In the next stage, the controller 16 operates the donor interfacepumps PP3/PP4 in the cassette 28 to draw a priming volume of storagesolution from the solution container 208 into the red blood cellcollection reservoir 308. This stage primes the tubing 278 between thecontainer 208 and the cassette 28, to minimize the volume of air pumpedinto the final red blood cell storage containers 307 and 309.

[0170] In the next stage, the controller 16 operates the donor interfacepumps PP3/PP4 in the cassette 28 to alternate pumping red blood cellsfrom the red blood cell collection reservoir 308 into the red blood cellcollection containers 307 and 309 (through the filter 313), with pumpingof red blood cell storage solution from the container 208 into the redblood cell collection containers 307 and 309 (also through the filter313). This alternating process mixes the storage solution with the redblood cells. The controller 16 counts the pneumatic pump strokes for redblood cells and the storage solution to obtain a desired ratio of redcell volume to storage solution volume (e.g., five pump strokes for redblood cells, followed by two pump strokes for storage solution, andrepeating the alternating sequence). This alternating supply of redblood cells and storage solution continues until the weigh scale for thered blood cell collection reservoir 308 indicates that the reservoir 308is empty.

[0171] When the red blood cell collection reservoir 308 is empty, thecontroller 16 operates the donor interface pumps PP3/PP4 to pumpadditional storage solution through the filter 313 and into the redblood storage containers 307 and 309, to ensure that a desired ratiobetween storage solution volume and red blood cell volume exists. Thisalso rinses residual red blood cells from the filter 313 into the redblood cell storage containers 307 and 309 to maximize post-filtrationpercent red blood cell recovery.

[0172] The controlled ratio of pump strokes for red blood cells and forstorage solution that the controller 16 achieves ensures that thestorage solution is always metered in at a constant ratio. Therefore,regardless of the volume of red blood cells collected, the final redblood cell/storage solution hematocrit can be constant.

[0173] The alternating supply of red blood cells and storage solutionthrough the filter 313 eliminates the need to first drain the storagesolution into the red blood cell collection reservoir 308, which lessensthe overall procedure time.

[0174] The alternating supply of red blood cells and storage solutionthrough the filter 313 also eliminates the need to manually agitate ared blood cell/storage solution mixture prior to leukofiltration. Due todensity differences, when concentrated red blood cells are added to apreservation solution, or vice versa, the preservation solution floatsto the top. Poorly mixed, high hematocrit, high viscosity red bloodcells lead to reduced flow rates during leukofiltration. Poorly mixed,high hematocrit, high viscosity red blood cell conditions can also leadto hemolysis. By alternating passage of red blood cells and storagesolution through the filter 313, mixing occurs automatically withoutoperator involvement.

[0175] The alternating supply of red blood cells and storage solutionthrough the filter 313 also eliminates the need to gravity drain the redblood cell product through the leukofilter 313. As a result, filtrationcan occur in about half the time required for a gravity-drain procedure.

[0176] If desired, the controller 16 can monitor weight changes relatingto the red blood cell collection reservoir 308 and the red blood cellstorage containers 307 and 309, to derive a value reflecting the percentof red blood cells that are recovered after passage through theleukofilter 313. This value can be communicated to the operator, e.g.,on the display screen of user the user interface.

[0177] The following expression can be used to derive the percentrecovery value:

[0178] % Recovery=[(Bag A Vol+Bag B Vol)/RBC Vol+Adsol)]* 100

[0179] where:

[0180] Bag A Vol represents the volume of red blood cells collected thecontainer 307, calculated as follows:

[0181] (Wt of Container 307 containing red blood cells(in g)—Container307 Tare)/1.062 g/ml

[0182] Bag B Vol represents the volume of red blood cells collected thecontainer 309, calculated as follows:

[0183] (Wt of Container 309 containing red blood cells(in g)—Container309 Tare)/1.062 g/ml

[0184] RBC Vol represents the volume of red blood cells collected in thered blood cell collection reservoir 308, which the controller 16determines by weight sensing at the end of the procedure.

[0185] Adsol represents the volume of red blood cell storage solutionadded to the during leukofiltration, which is determined by thecontroller 16 by capacitive sensing during processing.

[0186] (i) The Leukofilter

[0187] The leukofilter 313 can be variously constructed. In theembodiment illustrated in FIGS. 24A and 24B, the filter comprises ahousing 100 inclosing a filtration medium 102 that can comprise amembrane or be made from a fibrous material. The filtration medium 102can be arranged in a single layer or in a multiple layer stack. Iffibrous, the medium 102 can include melt blown or spun bonded syntheticfibers (e.g., nylon or polyester or polypropylene), semi-syntheticfibers, regenerated fibers, or inorganic fibers. If fibrous, the medium102 removes leukocytes by depth filtration. If a membrane, the medium102 removes leukocytes by exclusion.

[0188] The housing 100 can comprise rigid plastic plates sealed abouttheir peripheries. In the illustrated embodiment, the housing 100comprises first and second flexible sheets 104 of medical grade plasticmaterial, such as polyvinyl chloride plasticized withdi-2-ethylhexylphthalate (PVC-DEHP). Other medical grade plasticmaterials can be used that are not PVC and/or are DEHP-free.

[0189] In the illustrated embodiment, a unitary, continuous peripheralseal 106 (see FIG. 24B) is formed by the application of pressure andradio frequency heating in a single process to the two sheets 104 andfiltration medium 102. The seal 106 joins the two sheets 104 to eachother, as well as joins the filtration medium 102 to the two sheets 104.The seal 106 integrates the material of the filtration medium 102 andthe material of the plastic sheets 104, for a reliable, robust,leak-proof boundary. Since the seal 106 is unitary and continuous, thepossibility of blood shunting around the periphery of the filtrationmedium 102 is eliminated.

[0190] The filter 313 also includes inlet and outlet ports 108. Theports 108 can comprise tubes made of medical grade plastic material,like PVC-DEHP. In the embodiment shown in FIG. 24, the ports 108comprise separately molded parts that are heat sealed by radio frequencyenergy over a hole 109 formed in the sheets 104 (see FIG. 24B).

[0191] In the illustrated embodiment (as FIGS. 25A and 25B show), thefilter 313 is desirably placed within a restraining fixture 110 duringuse. The fixture 110 restrains expansion of the flexible sheets 104 ofthe filter housing 100 as a result of pressure applied by pumping redblood cells through the filter 313. The fixture 110 keeps the totalblood volume in the filter 313 at a minimum through the filtrationprocess, thereby decreasing filtration time, as well as increasing thered blood cell recovery percentage following leukofiltration.

[0192] The fixture 110 can take various forms. In the illustratedembodiment, the fixture 110 comprises two plates 112 coupled by a hinge114. The fixture 110 can be placed in an open condition (as FIG. 25Ashows) to receive the filter 313 prior to leukofiltration, or to removethe filter 313 following leukofiltration. The fixture 110 can also beplaced in a closed condition (as FIG. 25B shows) to sandwich the filter313 between the two plates 112. A releasably latch 116 holds the plates112 in the closed condition for use.

[0193] The plates 112 maintain a desired gap clearance, therebyrestraining expansion of the filter 313 during use. The gap clearance isselected to maintain a desired blood flow rate at a desired minimumblood volume.

[0194] The plates 112 desirably include indentations 118 in which theports 108 of the filter 313 rest in a non-occluded condition when thefixture 110 is closed. The interior surfaces of the plates 112 may beroughed or scored with a finish to aid blood flow through the filter 313when the fixture 110 is closed.

[0195] The fixture 110 can be made as a stand-alone item that can beseparately stored prior to use. It can be stored in association with thedevice 14 during transport and prior to use, e.g., in a receptacle 128formed on the exterior of the lid 40 of the device 14 (see FIG. 26). Thefixture 110 can include a mounting bracket 130 (see FIG. 28) that, e.g.,slidably engages a mating mounting track 132, to hold the fixture 110 inthe receptacle 128 prior to use (shown in phantom lines in FIG. 26) orto secure the fixture 110 on the base 38 as leukofiltration is carriedout (see FIG. 27).

[0196] It should be appreciated that pump-assisted leukofiltration ofred blood cells, whole blood, or other blood cell products, whereinblood flow through a leukofilter is not driven strictly by gravity flow,can be carried out using manual or automated systems havingconfigurations different than those shown in this Specification. Forexample, external peristaltic or fluid actuated pumping devices can beused to transfer whole blood or manually processed blood products fromseparation bags into processing or storage containers throughintermediate leukofiltration devices. It should also be appreciated thata filter restraining fixture of the type shown in FIG. 24B can also beused in association with any pump-assisted leukofiltration system. Itshould also be appreciated that a filter restraining fixture 110 canalso be used in systems where blood flow through the leukofilter reliesstrictly upon gravity flow.

[0197] The many features of the invention have been demonstrated bydescribing their use in separating whole blood into component parts forstorage and blood component therapy. This is because the invention iswell adapted for use in carrying out these blood processing procedures.It should be appreciated, however, that the features of the inventionequally lend themselves to use in other blood processing procedures.

[0198] For example, the systems and methods described, which make use ofa programmable cassette in association with a blood processing chamber,can be used for the purpose of washing or salvaging blood cells duringsurgery, or for the purpose of conducting therapeutic plasma exchange,or in any other procedure where blood is circulated in an extracorporealpath for treatment.

[0199] Features of the invention are set forth in the following claims.

We claim:
 1. A blood processing system comprising a blood processing setincluding a donor flow channel to convey blood from a donor, a bloodprocessing flow channel including a blood separation chamber tocentrifugally separate blood cells from donor whole blood, and a bloodcomponent collection flow channel including a blood cell storagecontainer and an in-line filter to remove leukocytes from the bloodcells before entering the blood cell storage container, the inlinefilter including a filter medium and a flexible housing enclosing thefilter medium, a blood processing device including a pump stationadapted to be placed into communication with the donor flow channel, theblood processing flow channel, and the blood component collection flowchannel, a centrifuge station adapted to support the blood separationchamber and to rotate the blood separation chamber, and a controller tooperate the pump station in multiple modes, including a processing mode,during which the pump station is operated to convey whole blood in thedonor flow channel into the blood processing flow channel for separationof the blood cells in the blood separation chamber, and a collectionmode, during which the pump station is operated to convey at least someof the blood cells in the blood processing flow channel into the bloodcomponent collection flow channel for on-line removal of leukocytes andcollection in the blood cell storage container, a fixture to restrainexpansion of the filter housing during operation of the pump station inthe collection mode, the fixture including a bracket to enablereleasably attachment of the fixture to the blood processing device. 2.A system according to claim 1 wherein the controller includes a functionto derive a value reflecting volume of blood cells present in the bloodcell storage container after passage through the filter as a percentageof volume of blood cells conveyed to the filter.
 3. A system accordingto claim 1 wherein the pump station includes a fluid pressure actuatedpump and an actuator to apply fluid pressure to the pump.
 4. A systemaccording to claim 1 wherein the blood processing device is mounted in acase sized to enable hand transport, and wherein the case includes areceptacle mating with the bracket to hold the fixture.
 5. A systemaccording to claim 1 wherein the blood processing device includes a baseand a lid hinged to the base, and wherein the case includes a holdermating with the bracket to hold the fixture.
 6. A system according toclaim 1 wherein the blood processing device includes a base and a lidhinged to the base, and wherein the lid includes a receptacle matingwith the bracket to store the fixture.
 7. A system according to claim 1wherein the blood cells comprise red blood cells.